ANALYSIS OF CELLULAR FACTORS AFFECTING RETROVIRUS INFECTION AND GROWTH

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This project has focused on the mechanisms of cellular restriction of retroviral growth in feline cells. It was previously shown that the feline endogenous virus, RD114, was restricted at a post-penetration level, rather than at the level of provirus integration and expression. Recent results show that this restriction is based on the restrictive cells' inability to completely process the major envelope glycoprotein of the RD114 virus, and the concurrent inability of RD114 particles containing unprocessed env products to initiate infection of non- permissive cells. This represents a novel mechanism of virus restriction. Results also suggest, however, that certain cells can be infected by such viruses and that complete env processing is not an absolute requirement for viral infectivity. Restriction of lymphotropic feline lentiviruses in adherent cells through the analysis of a series of chimeric virus constructs involving clones of the Petaluma strain of FIV, which replicates in adherent cells, and the PPR strain, which is lymphotropic, have also been investigated. Results indicate that a block involving the viral env gene, most probably involving a cell receptor, blocks PPR's ability to spread in adherent cells. However, evidence also suggests that PPR expression is suppressed in non-adherent cells at a post-penetration level, implying a second block to infection in restrictive cells.